The long-term objective of this research is to understand the link between NMDA receptor activation and dendritic spine morphological changes by studying proteins that interact with the NMDA receptor. Specifically, this research will characterize the interaction between the non-kinase phorbol ester receptor, alpha-chimaerin and the NMDA receptor subunit NR2A, and study how alpha-chimaerin affects spine morphology during long-term potentiation (LTP). Co-immunoprecipitation experiments will be used to confirm the interaction between alpha-chimaerin and NR2A, including the conditions that modulate this interaction. Fluorescently labeled proteins and small interfering RNA constructs targeting alpha-chimaedn will be used, along with fluorescent microscopy, to study spine shape and dynamics in the presence of overexpressed alpha-chimaerin and in the absence of alpha-chimaerin. This research should elucidate the mechanisms by which NMDA receptor activation produces changes in dendritic spine morphology and allow greater understanding of the causes of conditions, such as mental retardation, in which LTP and spine shape are distorted.